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. 2025 May 1;28(3):333-343.
doi: 10.4103/aian.aian_547_24. Epub 2025 May 9.

The Efficacy of Anti-amyloid Monoclonal Antibodies in Early Alzheimer's Dementia: A Systematic Review

Alyaa Mostafa  1 , Stephanie Tiu  2 , Farooq Khan  3   4   5 , Nusrath A Baig  3
Affiliations

The Efficacy of Anti-amyloid Monoclonal Antibodies in Early Alzheimer's Dementia: A Systematic Review

Alyaa Mostafa et al. Ann Indian Acad Neurol. .

Abstract

Introduction: Much research has been conducted into the role and safety of anti-amyloid monoclonal antibodies on the progression of Alzheimer's disease (AD). Despite the historical approval of three drugs by the US Food and Drug Administration for the treatment of early AD, there remains other potential treatment, which is yet to be approved or further developed. This systematic review explores the efficacy of anti-amyloid monoclonal antibodies in the treatment of early AD from reported clinical trials.

Methods: Authors conducted a systematic search of MEDLINE and Embase. Screening was carried out by two authors and cross-checked thereafter. Clinical changes in cognition and objective measures such as cerebrospinal fluid biomarkers and imaging constituted primary and secondary outcomes, respectively.

Results: Our search yielded 14 randomized controlled trials; the primary focus of the included trials is amyloid-β. The monoclonal antibodies reported in this review are: lecanemab, aducanumab, crenezumab, solanezumab, donanemab, bapineuzumab, and gantenerumab. The most common finding among the trials is the lack of statistically significant results in measures of clinical outcomes, (e.g., Clinical Dementia Rating Scale-Sum of Boxes, AD Assessment Scale-Cognitive Subscale). However, specific trials investigating lecanemab, aducanumab, and donanemab demonstrated promising improvements in clinical cognition. Results related to secondary outcomes were also mixed, but showed more positive findings across the included trials. Overall, primary outcomes were inconsistent with secondary outcomes.

Conclusion: Our findings highlight the need to consider the complex pathophysiology of AD in treatment development. Focusing solely on the amyloid-beta hypothesis may be inadequate; further research is necessary to understand the underlying mechanisms and develop treatments for the multifactorial nature of the disease.

Keywords: Alzheimer’s dementia; anti-amyloid antibodies; clinical outcomes; early Alzheimer’s disease; mild cognitive impairment; monoclonal antibodies.

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Conflict of interest statement

FK was paid honorarium by Biogen, makers of Aducanumab, for developing educational material for the company. The remaining authors (AM, ST, and NA) have nothing to disclose. This study presents independent research by the named authors.

Figures

Figure 1
Figure 1
PRSIMA flowchart showing the selection process *Automated filters: limit to papers from 2013 to current, English Language, clinical trial, Phase 3 or clinical trial, or clinical trial or randomized controlled trial. RCT: randomized controlled trial
See this image and copyright information in PMC

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